Alex Soltermann

Dysfunctional DNA repair with subsequent genome instability and high mutational burden represents a major hallmark of cancer. In established malignant tumors, increased DNA repair capacity mediates resistance to DNA-damaging therapeutics, including cytotoxic drugs, radiotherapy, and selected small molecules including inhibitors of poly (ADP-ribose) polymerase (PARP), Ataxia Telangiectasia Mutated (ATM), ataxia telangiectasia and Rad3-related protein (ATR), and Wee1 kinase (Wee1). In addition, DNA repair deficiency is not only associated with sensitivity to selected anticancer drugs, but also with increased mutagenicity and increased neoantigen load on tumor cells, resulting in increased immunogenicity and improved response to CTLA4- or PD-(L)1 targeting monoclonal antibodies. DNA damage response (DDR) is composed of complex signalling pathways, including the sensing of the DNA damage, signal transduction, cellular response pathways to DNA damage, and activation of DNA repair. DNA double strand breaks (DSBs) are the most dangerous form of DNA damage. Tumor cells are characterised by frequent accumulation of DSBs caused by either endogenous replication stress or the impact of cancer treatment, most prominently chemotherapy and radiotherapy. Therefore, response of cancer cells to DSBs represents a crucial mechanism for how tumors respond to systemic treatment or radiotherapy, and how resistance develops. Ample clinical evidence supports the importance of DDR associated kinases as predictive and prognostic biomarkers in cancer patients. The ATM-CHK2 and ATR-CHK1-WEE1 pathways initiate DNA DSB repair. In the current review, we focus on major DDR associated kinases including ATM, ATR, CHK1, CHK2, and WEE1, and discuss their potential prognostic and predictive value in solid malignancies.

Introduction: Pulmonary hypertension is a common complication in patients with severe chronic obstructive pulmonary disease (COPD) but the pathogenesis of its development is not completely understood. MicroRNAs (miRNAs) are small, non-coding gene regulators that have been associated with the pathogenesis of pulmonary hypertension. Here we investigated the signature from miRNAs in lung tissue slides from patients with end-stage COPD with and without elevated pulmonary pressure. Methods: Paraffin-embedded lung tissue specimens from COPD patients undergoing lung volume reduction surgery (LVRS) or lung transplantation were used. Pulmonary hemodynamics was invasively assessed in all patients before surgery. miRNA isolation was performed using the recoverall total nucleic acid isolation kit (Ambion ®) and quantified by qPCR. Results: 11 miRNAs previously associated with the pathogenesis of pulmonary hypertension were analysed. Significantly decreased expression levels of miR-125a (-0.54±0.33 vs 0.01±0.65, pConclusion: This is the first report on the miRNA profile of COPD patients with and without pulmonary hypertension showing that most miRNAs are downregulated in patients with PH-COPD. Further studies are needed to answer the question whether this miRNA profile can be employed as predictor for the presence of an elevated pulmonary pressure in COPD patients.

There is evidence that oregano essential oil has a significant antioxidant effect on the process of lipid oxidation. In order to obtain fractions enriched in antioxidant properties, oregano essential oil samples were processed by molecular distillation. Molecular distillation experiments were done in two groups of tests, using an evaporating temperature between 22 and 30 ºC. Pressure was varied between 0.7 and 53 mbar. Antioxidant activity, specifically radical scavenging capacity, was analyzed in the essential oil and the distillates and residues obtained by a free radical scavenging method, using DPPH* (2,2-diphenyl-1picrylhydrazyl). The results obtained allowed to conclude that the free radical scavenging capacity was increased in the residue fractions obtained by molecular distillation. These fractions were concentrated in thymol. The IC50 values of the residues were similar to the synthetic antioxidant BHT, suggesting that fractions concentrated in oxygen derivatives obtained by molecular distillation could be used in the food industry to retard lipid degradation.